Analysis of the miRNA content of microvesicles and exosomes released from two different human melanoma cell lines upon activation of a purinergic receptor.. P2X7 receptor favors melanoma metastasis and causes the release of miRNA-containing exosomes and microvesicles from cancer cells.

The tumor microenvironment (TME) is rich in components that strongly influence cancer cell survival affecting interaction with immune and stroma cells, extravasation, and dissemination. One of the key molecules present in the tumor milieu is ATP, which is not only highly concentrated in the microenvironment but also has a role in the promotion of cancer growth and spreading mainly via its receptor P2X7.MicroRNAs (miRNAs) are small non-coding RNA molecules, which regulate transcriptional and post-transcriptional gene expression and are often contained in MVs released from cancer cells. Analysis by small RNA sequencing of the miRNA content of small and large vesicles obtained from both Sk-Mel-28 and Ma-Mel-19 cells, before and after ATP stimulation, shows a different global miRNA expression profile.ATP stimulation of the receptor caused differential expression of: 251 miRNAs in Sk-Mel-28 small vesicles; 193 miRNAs in Sk-Mel-28 large vesicles; 91 miRNAs in Ma-Mel-19 small vesicles; 206 miRNAs in Ma-Mel-19 large vesicles. These data show a profound alteration of the miRNA content of MVs released by human melanoma cells following P2X7 stimulation.